View source for L-DOPA

{{Short description|Chemical compound}}
{{About|<small>L</small>-DOPA as a biological compound|its role as a medication and supplement|Levodopa}}
{{cs1 config|name-list-style=vanc|display-authors=6}}
{{DISPLAYTITLE:<small>L</small>-DOPA}}
{{Use dmy dates|date=September 2024}}

{{Chembox
<!-- Images -->
| ImageFile = 3,4-Dihydroxy-L-phenylalanin (Levodopa).svg
| ImageSize = 
| ImageClass = skin-invert
| ImageCaption = [[Skeletal formula]] of <small>L</small>-DOPA
| ImageFile2 = L-DOPA-from-xtal-view-2-3D-bs-17.png
| ImageSize2 = 180px
| ImageCaption2 = [[Ball-and-stick model]] of the [[zwitterion]]ic form of <small>L</small>-DOPA found in the [[crystal structure]]<ref>{{ cite journal | title = Experimental and theoretical determination of electronic properties in Ldopa | vauthors = Howard ST, Hursthouse MB, Lehmann CW, Poyner EA | journal = [[Acta Crystallographica|Acta Crystallogr. B]] | volume = 51 | pages = 328–337 | year = 1995 | issue = 3 | doi = 10.1107/S0108768194011407 | bibcode = 1995AcCrB..51..328H | s2cid = 96802274 }}</ref>
<!-- Names -->
| IUPACName = (''S'')-2-Amino-3-(3,4-dihydroxyphenyl)propanoic acid
| OtherNames = {{sm|l}}-3,4-Dihydroxyphenylalanine; Levodopa
<!-- Sections -->
| Section1 = {{Chembox Identifiers
| CASNo = 59-92-7
| ChEBI = 15765
| ChEMBL = 1009
| ChemSpiderID = 5824
| DrugBank = DB01235
| EINECS = 200-445-2
| EC_number = 
| InChI = 1S/C9H11NO4/c10-6(9(13)14)3-5-1-2-7(11)8(12)4-5/h1-2,4,6,11-12H,3,10H2,(H,13,14)/t6-/m0/s1
| InChIKey = WTDRDQBEARUVNC-LURJTMIESA-N
| KEGG = C00355
| MeSHName = 
| PubChem = 6047
| SMILES = C1=CC(=C(C=C1C[C@@H](C(=O)O)N)O)O
| UNII = 46627O600J
  }}
| Section2 = {{Chembox Properties
| C=9 | H=11 | N=1 | O=4
| MolarMass = 197.19 g/mol
| Appearance = 
| Density = 
| MeltingPt = 
| BoilingPt = 
| Solubility = 
  }}
| Section3 = {{Chembox Hazards
| MainHazards = 
| FlashPt = 
| AutoignitionPt = 
  }}
}}

'''{{sm|l}}-DOPA''', also known as '''{{sm|l}}-3,4-dihydroxyphenylalanine''' and used medically as '''levodopa''', is made and used as part of the normal [[biology]] of some plants<ref name="JAMANeuro">{{cite journal | vauthors = Cohen PA, Avula B, Katragunta K, Khan I | title = Levodopa Content of Mucuna pruriens Supplements in the NIH Dietary Supplement Label Database | journal = JAMA Neurology | volume = 79 | issue = 10 | pages = 1085–1086 | date = October 2022 | pmid = 35939305 | doi = 10.1001/jamaneurol.2022.2184 | pmc = 9361182 }}</ref> and animals, including humans. Humans, as well as a portion of the other animals that utilize {{sm|l}}-DOPA, make it via [[biosynthesis]] from the [[amino acid]] [[L-tyrosine|{{sm|l}}-tyrosine]].

{{sm|l}}-DOPA is the [[precursor (chemistry)|precursor]] to the [[neurotransmitter]]s [[dopamine]], [[norepinephrine]] (noradrenaline), and [[epinephrine]] (adrenaline), which are collectively known as [[catecholamine]]s. Furthermore, {{sm|l}}-DOPA itself mediates [[Neurotrophic factors|neurotrophic factor]] release by the brain and [[central nervous system]].<ref>{{cite journal | vauthors = Lopez VM, Decatur CL, Stamer WD, Lynch RM, McKay BS | title = L-DOPA is an endogenous ligand for OA1 | journal = PLOS Biology | volume = 6 | issue = 9 | article-number = e236 | date = September 2008 | pmid = 18828673 | pmc = 2553842 | doi = 10.1371/journal.pbio.0060236 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Hiroshima Y, Miyamoto H, Nakamura F, Masukawa D, Yamamoto T, Muraoka H, Kamiya M, Yamashita N, Suzuki T, Matsuzaki S, Endo I, Goshima Y | title = The protein Ocular albinism 1 is the orphan GPCR GPR143 and mediates depressor and bradycardic responses to DOPA in the nucleus tractus solitarii | journal = British Journal of Pharmacology | volume = 171 | issue = 2 | pages = 403–14 | date = January 2014 | pmid = 24117106 | pmc = 3904260 | doi = 10.1111/bph.12459 }}</ref> In some plant families (of the order [[Caryophyllales]]), {{sm|l}}-DOPA is the central precursor of a biosynthetic pathway that produces a class of pigments called [[betalain]]s.<ref>{{cite journal |vauthors= Polturak G, Breitel D, Grossman N, Sarrion-Perdigones A, Weithorn E, Pliner M, Orzaez D, Granell A, Rogachev I, Aharoni A |title=Elucidation of the first committed step in betalain biosynthesis enables the heterologous engineering of betalain pigments in plants |journal= New Phytol |volume=210 |issue=1 |pages= 269–283 |year=2016 |doi=10.1111/nph.13796 |doi-access=free |pmid=26683006 |bibcode=2016NewPh.210..269P |hdl=10251/87415 |hdl-access=free }}</ref>

{{sm|l}}-DOPA can be manufactured and in its pure form is sold as a [[drug]] with the {{Abbrlink|INN|International Nonproprietary Name}} ''[[levodopa]]''. As a drug, it is used in the [[therapy|treatment]] of [[Parkinson's disease]] and [[dopamine-responsive dystonia]], as well as [[restless leg syndrome]].<ref>{{cite journal |last1=Scholz |first1=Hanna |last2=Trenkwalder |first2=Claudia |last3=Kohnen |first3=Ralf |last4=Kriston |first4=Levente |last5=Riemann |first5=Dieter |last6=Hornyak |first6=Magdolna |title=Levodopa for the treatment of restless legs syndrome |journal=Cochrane Database of Systematic Reviews |date=15 February 2011 |volume=2011 |issue=5 |article-number=CD005504 |doi=10.1002/14651858.CD005504.pub2 |pmid=21328278 |s2cid=196338172 |pmc=8889887 }}</ref>

{{sm|l}}-DOPA has a counterpart with opposite [[chirality (chemistry)#By configuration: D- and L-|chirality]], [[D-DOPA|{{sm|d}}-DOPA]]. As is true for many molecules, the human body produces only one of these [[isomer]]s (the {{sm|l}}-DOPA form). The [[Enantiomer|enantiomeric purity]] of {{sm|l}}-DOPA may be analyzed by determination of the optical rotation or by chiral [[thin-layer chromatography]].<ref>{{cite journal | vauthors = Martens J, Günther K, Schickedanz M | title = Resolution of Optical Isomers by Thin-Layer Chromatography: Enantiomeric Purity of Methyldopa | journal = [[Arch. Pharm.]] | volume = 319 | issue = 6 | pages = 572–574 | date = 1986 | doi = 10.1002/ardp.19863190618 | s2cid = 97903386 }}</ref>

==Biological role==
{{Phenylalanine biosynthesis|align=right}}
{{sm|l}}-DOPA is produced from the amino acid {{sm|l}}-[[tyrosine]] by the enzyme [[tyrosine hydroxylase]]. {{sm|l}}-DOPA can act as an {{sm|l}}-tyrosine mimetic and be incorporated into proteins by mammalian cells in place of {{sm|l}}-tyrosine, generating [[protease]]-resistant and [[protein aggregation|aggregate-prone proteins]] ''in vitro'' and may contribute to [[neurotoxicity]] with chronic {{sm|l}}-DOPA administration.<ref>{{cite journal | vauthors = Rodgers KJ | title = Non-protein amino acids and neurodegeneration: the enemy within | journal = Experimental Neurology | volume = 253 | pages = 192–196 | date = March 2014 | pmid = 24374297 | doi = 10.1016/j.expneurol.2013.12.010 | s2cid = 2288729 }}</ref>
It is also the precursor for the [[monoamine]] or [[catecholamine]] neurotransmitters dopamine, norepinephrine (noradrenaline), and epinephrine (adrenaline). Dopamine is formed by the decarboxylation of {{sm|l}}-DOPA by [[aromatic L-amino acid decarboxylase|aromatic {{sm|l}}-amino acid decarboxylase]] (AADC).

{{sm|l}}-DOPA can be directly metabolized by [[catechol-O-methyl transferase|catechol-''O''-methyl transferase]] to [[3-O-methyldopa|3-''O''-methyldopa]], and then further to [[vanillactic acid]]. This metabolic pathway is nonexistent in the healthy body, but becomes important after peripheral {{sm|l}}-DOPA administration in patients with Parkinson's disease or in the rare cases of patients with AADC enzyme deficiency.<ref name="pmid1281049">{{cite journal | vauthors = Hyland K, Clayton PT | title = Aromatic L-amino acid decarboxylase deficiency: diagnostic methodology | journal = Clinical Chemistry | volume = 38 | issue = 12 | pages = 2405–10 | date = December 1992 | pmid = 1281049 | doi =  10.1093/clinchem/38.12.2405| url = http://www.clinchem.org/cgi/reprint/38/12/2405.pdf | access-date = 16 October 2008 | archive-url = https://web.archive.org/web/20110607122144/http://www.clinchem.org/cgi/reprint/38/12/2405.pdf | archive-date = 7 June 2011 | doi-access = free }}</ref>

{{sm|l}}-Phenylalanine, {{sm|l}}-tyrosine, and {{sm|l}}-DOPA are all precursors to the biological [[pigment]] [[melanin]]. The enzyme [[tyrosinase]] [[catalyst|catalyzes]] the [[oxidation]] of {{sm|l}}-DOPA to the reactive intermediate [[dopaquinone]], which reacts further, eventually leading to melanin [[oligomer]]s. In addition, [[tyrosinase]] can convert tyrosine directly to {{sm|l}}-DOPA in the presence of a reducing agent such as [[ascorbic acid]].<ref>{{cite journal | vauthors = Ito S, Kato T, Shinpo K, Fujita K | title = Oxidation of tyrosine residues in proteins by tyrosinase. Formation of protein-bonded 3,4-dihydroxyphenylalanine and 5-S-cysteinyl-3,4-dihydroxyphenylalanine | journal = The Biochemical Journal | volume = 222 | issue = 2 | pages = 407–11 | date = September 1984 | pmid = 6433900 | pmc = 1144193 | doi = 10.1042/bj2220407 }}</ref>

==Chemistry==
<small>L</small>-DOPA, also known as <small>L</small>-3,4-dihydroxyphenylalanine or <small>L</small>-3-hydroxytyrosine, is an [[aromatic amino acid]] derived from [[phenylalanine|<small>L</small>-phenylalanine]] and [[tyrosine|<small>L</small>-tyrosine]]. It is a [[substituted phenethylamine|phenethylamine]], [[monoamine]], and [[catecholamine]], and is a [[precursor (biochemistry)|biological precursor]] of the [[neurotransmitter]]s [[dopamine]] (3,4-dihydroxyphenethylamine), [[norepinephrine]] (3,4,β-trihydroxyphenethylamine), and [[epinephrine]] (3,4,β-trihydroxy-''N''-methylphenethylamine).

===Synthesis===
: [[File:L-dopaSyn.svg|class=skin-invert-image|thumb|center|550px|Synthesis of {{sm|l}}-DOPA via hydrogenation with C<sub>2</sub>-symmetric diphosphine.]]

==History==
{{sm|l}}-DOPA was first isolated from the seeds of the ''[[Vicia faba]]'' (broad bean) plant in 1913 by Swiss biochemist Markus Guggenheim.<ref>{{cite journal | vauthors = Ovallath S, Sulthana B | title = Levodopa: History and Therapeutic Applications | journal = Annals of Indian Academy of Neurology | volume = 20 | issue = 3 | pages = 185–189 | date = 2017 | pmid = 28904446 | pmc = 5586109 | doi = 10.4103/aian.AIAN_241_17 | doi-access = free }}</ref>

The 2001 [[Nobel Prize in Chemistry]] was also related to {{sm|l}}-DOPA: the Nobel Committee awarded one-quarter of the prize to [[William S. Knowles]] for his work on chirally catalysed [[hydrogenation]] reactions, the most noted example of which was used for the synthesis of {{sm|l}}-DOPA.<ref>{{cite journal | doi = 10.1021/ar00087a006 | title = Asymmetric hydrogenation | year = 1983 | vauthors = Knowles WS | journal = Accounts of Chemical Research | volume = 16 | issue = 3 | pages = 106–112}}</ref><ref>{{cite web | url = http://www.chem.wisc.edu/areas/reich/syntheses/dopa-monsanto-knowles.htm | title = Synthetic scheme for total synthesis of DOPA, L- (Monsanto) | publisher = UW Madison, Department of Chemistry | access-date = 30 September 2013}}</ref><ref>{{cite journal| vauthors = Knowles WS |title=Application of organometallic catalysis to the commercial production of L-DOPA|journal=Journal of Chemical Education|date=March 1986|volume=63|issue=3|page=222|doi=10.1021/ed063p222|bibcode=1986JChEd..63..222K}}</ref>

== Other organisms ==
=== Marine adhesion ===
{{sm|l}}-DOPA is a key [[chemical compound|compound]] in the formation of [[marine adhesive protein]]s, such as those found in [[mussel]]s.<ref>{{cite journal | vauthors = Waite JH, Andersen NH, Jewhurst S, Sun C | title=Mussel Adhesion: Finding the Tricks Worth Mimicking | journal=J Adhesion | volume=81 | year=2005 | pages=1–21 | doi=10.1080/00218460590944602 | issue=3–4 | s2cid=136967853 }}</ref><ref>{{cite web | url = https://www.sciencedaily.com/releases/2006/08/060816024159.htm | title = Study Reveals Details Of Mussels' Tenacious Bonds | publisher = Science Daily | date = 16 August 2006 | access-date = 30 September 2013}}</ref> It is believed to be responsible for the water-resistance and rapid curing abilities of these proteins. {{sm|l}}-DOPA may also be used to prevent surfaces from fouling by bonding antifouling polymers to a susceptible [[substrate (biochemistry)|substrate]].<ref>{{cite web | url = http://biomaterials.bme.northwestern.edu/mussel.asp | title = Mussel Adhesive Protein Mimetics | archive-url = https://web.archive.org/web/20060529181142/http://biomaterials.bme.northwestern.edu/mussel.asp | archive-date=29 May 2006 }}</ref> The versatile chemistry of {{sm|l}}-DOPA can be exploited in nanotechnology.<ref>{{cite journal | vauthors = Giuri D, Ravarino P, Tomasini C | title = L-Dopa in small peptides: an amazing functionality to form supramolecular materials | journal = Organic & Biomolecular Chemistry | volume = 19 | issue = 21 | pages = 4622–4636 | date = June 2021 | pmid = 33978030 | doi = 10.1039/D1OB00378J | s2cid = 234474122 | hdl = 11585/840774 | hdl-access = free }}</ref>  For example, DOPA-containing self-assembling peptides were found to form functional nanostructures, adhesives and gels.<ref>{{cite journal | vauthors = Fichman G, Adler-Abramovich L, Manohar S, Mironi-Harpaz I, Guterman T, Seliktar D, Messersmith PB, Gazit E | title = Seamless metallic coating and surface adhesion of self-assembled bioinspired nanostructures based on di-(3,4-dihydroxy-L-phenylalanine) peptide motif | journal = ACS Nano | volume = 8 | issue = 7 | pages = 7220–7228 | date = July 2014 | pmid = 24936704 | pmc = 4108209 | doi = 10.1021/nn502240r | bibcode = 2014ACSNa...8.7220F }}</ref><ref>{{cite journal | vauthors = Fichman G, Guterman T, Adler-Abramovich L, Gazit E | title = The Use of the Calcitonin Minimal Recognition Module for the Design of DOPA-Containing Fibrillar Assemblies | journal = Nanomaterials | volume = 4 | issue = 3 | pages = 726–740 | date = August 2014 | pmid = 28344244 | pmc = 5304689 | doi = 10.3390/nano4030726 | doi-access = free }}</ref><ref>{{cite journal | vauthors = Fichman G, Andrews C, Patel NL, Schneider JP | title = Antibacterial Gel Coatings Inspired by the Cryptic Function of a Mussel Byssal Peptide | journal = Advanced Materials | volume = 33 | issue = 40 | pages = e2103677 | date = October 2021 | article-number = 2103677 | pmid = 34423482 | pmc = 8492546 | doi = 10.1002/adma.202103677 | bibcode = 2021AdM....3303677F }}</ref><ref>{{cite journal | vauthors = Maity S, Nir S, Zada T, Reches M | title = Self-assembly of a tripeptide into a functional coating that resists fouling | journal = Chemical Communications | volume = 50 | issue = 76 | pages = 11154–11157 | date = October 2014 | pmid = 25110984 | doi = 10.1039/C4CC03578J }}</ref>

=== Plants and in the environment ===
In plants, <small>L</small>-DOPA functions as an [[allelochemical]] which inhibits the growth of certain species, and is produced and secreted by a few legume species such as the broad bean ''[[Vicia faba]]'' and the velvet bean ''[[Mucuna pruriens]]''.<ref>{{cite journal | vauthors = Fujii Y, Shibuya T, Yasuda T| title = L-3,4-Dihydroxyphenylalanine as an Allelochemical Candidate from Mucuna pruriens (L.) DC. var. utilis | journal = Agricultural and Biological Chemistry | volume = 55 | issue = 2 | pages = 617–618 | date = 1991 | doi = 10.1080/00021369.1991.10870627 | doi-access = free }}</ref> Its effect is strongly dependent on the pH and the reactivity of iron in the soil.<ref>{{cite journal | vauthors = Hsieh EJ, Liao SW, Chang CY, Tseng CH, Wang SL, Grillet L| title = L-DOPA induces iron accumulation in roots of Ipomoea aquatica and Arabidopsis thaliana in a pH-dependent manner | journal = Botanical Studies | volume = 64 | issue = 24 | pages = 617–618 | date = 2023 | article-number = 24 | pmid = 37620733 | pmc = 10449704 | doi = 10.1186/s40529-023-00396-7 | doi-access = free | bibcode = 2023BotSt..64...24H }}</ref> <small>L</small>-DOPA can also be found in [[Cephalopod ink|cephalopod ink.]]<ref>{{Cite journal |last1=Lucero |first1=M. T. |last2=Farrington |first2=H. |last3=Gilly |first3=W. F. |date=August 1994 |title=Quantification of L-Dopa and Dopamine in Squid Ink: Implications for Chemoreception |journal=The Biological Bulletin |volume=187 |issue=1 |pages=55–63 |doi=10.2307/1542165 |jstor=1542165 |issn=1939-8697 |pmid=29281314}}</ref>

== Use as a medication and supplement ==
{{Main|Levodopa}}

<small>L</small>-DOPA is used medically under the name ''[[levodopa]]'' in the treatment of [[Parkinson's disease]] and certain other medical conditions. It is usually used in [[combination drug|combination]] with a [[peripherally selective drug|peripherally selective]] [[aromatic L-amino acid decarboxylase|aromatic <small>L</small>-amino acid decarboxylase]] (AAAD) [[aromatic L-amino acid decarboxylase inhibitor|inhibitor]] such as [[carbidopa]] or [[benserazide]]. These agents increase the strength and duration of levodopa. Combination formulations include [[levodopa/carbidopa]] and [[levodopa/benserazide]], as well as [[levodopa/carbidopa/entacapone]].

<small>L</small>-DOPA is found in high amounts in ''[[Mucuna pruriens]]'' (velvet bean) and is available and used [[over-the-counter drug|over-the-counter]] as a [[dietary supplement|supplement]].

== References ==
{{Reflist}}

{{Supplements}}
{{Amino acids}}
{{Amino acid metabolism enzymes}}
{{Neurotransmitter metabolism intermediates}}
{{Dopamine receptor modulators}}
{{Phenethylamines}}

{{DEFAULTSORT:DOPA, L-}}

[[Category:Alpha-Amino acids]]
[[Category:Aromatic amino acids]]
[[Category:Carbonic anhydrase activators]] <!--https://www.ncbi.nlm.nih.gov/pubmed/29478330-->
[[Category:Catecholamines]]
[[Category:Dopamine agonists]]
[[Category:Monoamine precursors]]